Roles of ASIC3, TRPV1, and NaV 1.8 in the transition from acute to chronic pain in a mouse model of fibromyalgia

• Published in: Molecular pain Vol. 10
• Main Authors: Chen, Wei-Nan, Lee, Cheng-Han, Lin, Shing-Hong, Wong, Chia-Wen, Sun, Wei-Hsin, Wood, John N, Chen, Chih-Cheng
• Format: Journal Article
• Language: English
• Published: London Sage Publications Ltd 01.01.2014
• Subjects: Acids; Biomedical research; Experiments; Fibromyalgia; Kinases; Life sciences; Muscle pain; Proteins; Rodents
• ISSN: 1744-8069
• DOI: 10.1186/1744-8069-10-40

Doc number: 40 Abstract Background: Tissue acidosis is effective in causing chronic muscle pain. However, how muscle nociceptors contribute to the transition from acute to chronic pain is largely unknown. Results: Here we showed that a single intramuscular acid injection induced a priming effect on muscle nociceptors of mice. The primed muscle nociceptors were plastic and permitted the development of long-lasting chronic hyperalgesia induced by a second acid insult. The plastic changes of muscle nociceptors were modality-specific and required the activation of acid-sensing ion channel 3 (ASIC3) or transient receptor potential cation channel V1 (TRPV1). Activation of ASIC3 was associated with increased activity of tetrodotoxin (TTX)-sensitive voltage-gated sodium channels but not protein kinase C... (PKC...) in isolectin B4 (IB4)-negative muscle nociceptors. In contrast, increased activity of TTX-resistant voltage-gated sodium channels with ASIC3 or TRPV1 activation in NaV 1.8-positive muscle nociceptors was required for the development of chronic hyperalgesia. Accordingly, compared to wild type mice, NaV 1.8-null mice showed briefer acid-induced hyperalgesia (5 days vs. >27 days). Conclusion: ASIC3 activation may manifest a new type of nociceptor priming in IB4-negative muscle nociceptors. The activation of ASIC3 and TRPV1 as well as enhanced NaV 1.8 activity are essential for the development of long-lasting hyperalgesia in acid-induced, chronic, widespread muscle pain.